title: Beneficial effects of vildagliptin combined with miglitol on glucose tolerance and islet morphology in diet-controlled db/db mice.
abstract: Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control in patients with type 2 diabetes primarily by increasing plasma active glucagon-like peptide-1 (GLP-1) levels. While various combination therapies based on DPP-4 inhibitors have been proposed for treatment of type 2 diabetes, the effects of combination therapy of DPP-4 inhibitors and alpha-glucosidase inhibitors on β-cell function are less characterized. We evaluated the effects of long-term treatment with vildagliptin, a DPP-4 inhibitor, on metabolic parameters and β-cell function, in combination with miglitol, an alpha-glucosidase inhibitor, in diet-controlled db/db mice. In this study, 6-week-old male db/db mice were provided with standard chow twice a day for 6 weeks. Meal tolerance tests and glucose tolerance tests showed that the combination therapy of vildagliptin with miglitol, but not each alone, suppressed postprandial glycemic excursion, enhanced postprandial active GLP-1 levels and prevented deterioration of glucose tolerance in the db/db mice. The combination treatment did not alter β-cell mass, but resulted in preserved expression of glucose transporter 2, Zinc transporter 8 and MafA and reduced the number of α cells. These results suggest that the combination of vildagliptin and miglitol prevents the development of overt diabetes in diet-controlled pre-diabetic db/db mice by normalizing postprandial glucose and incretin response, and by preserving β-cell structure and the expression of factors essential for β-cell function.
authors.affiliation: Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Ishibashi
authors.forename: Akemi
authors.initials: A
authors.lastname: Hara
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujitani
authors.forename: Toyoyoshi
authors.initials: T
authors.lastname: Uchida
authors.forename: Koji
authors.initials: K
authors.lastname: Komiya
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Tamaki
authors.forename: Hiroko
authors.initials: H
authors.lastname: Abe
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ogihara
authors.forename: Akio
authors.initials: A
authors.lastname: Kanazawa
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Kawamori
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watada
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004032:Diet; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009570:Nitriles / Q000627:therapeutic use*; D011759:Pyrrolidines / Q000627:therapeutic use*; D000077597:Vildagliptin
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D009570:Nitriles; D011759:Pyrrolidines; C045621:miglitol; D017485:1-Deoxynojirimycin; D000077597:Vildagliptin; D000218:Adamantane
keywords: Alpha-glucosidase inhibitor; DPP-4; DPP-4 inhibitor; GLP-1; IPGTT; Incretin; Miglitol; Type 2 diabetes; Vildagliptin; dipeptidyl peptidase-4; glucagon-like peptide-1; intraperitoneal glucose tolerance test